Session Information
Session Title: Rheumatoid Arthritis - Clinical Aspects: Novel Biomarkers and Other Measurements of Disease Activity
Session Type: Abstract Submissions (ACR)
Background/Purpose
RF and ACPA are used for early diagnosis and in prediction models for the risk of RA development in arthralgia patients. There remains a high unmet need for biomarkers in the earliest stages of RA to assist with detection and prognosis to enable therapy initiation within the first 6-12 weeks of symptom onset. The 14-3-3η serum protein and its corresponding anti-14-3-3η auto-antibodies are early complementary markers to RF/ACPA. This study describes their expression and diagnostic utility as well as their complementarity to RF/ACPA in early RA.
Methods
14-3-3η plasma protein levels were measured on the Augurex ELISA and 14-3-3η auto-antibody levels on the Meso-Scale-Discovery electro-chemiluminescent platform in 409 consecutive early RA patients (Reade cohort) according to the 2010 ACR/EULAR RA classification criteria. Patients were DMARD-naïve, had a rheumatologist-confirmed diagnosis, median symptom duration was 4 months, mean age was 54 years and 73% were female. For 14-3-3η auto-antibody level determination, a composite score of six (6) peptides was generated. Peptides were selected based on their individual highest sensitivity for 100% specificity and their complementarity to maximize patient capture. An auto-antibody score of ≥380 U/ml was determined to be the best positive cut-off. Serum 14-3-3η protein levels were previously determined in these subjects with a positive diagnostic cut-off of > 0.19 ng/ml. Positive baseline status for each of the 14-3-3η markers and RF and ACPA were compared to examine the extent of early RA patient capture rate versus RF/ACPA.
Results
In the 409 patients, 67% (n=275) were positive for the 14-3-3η protein with median (IQR) titres of 0.63 (0.10-5.13) ng/ml and 77% (n=313) were positive for 14-3-3η auto-antibodies with median (IQR) values of 527 (387-753) U/ml. RF and ACPA positive rates in this cohort were 63% (n=259) and 69% (n=282), respectively. 76% (n=310) of patients were positive for one or both of RF and ACPA, 93% (n=394) were positive for either of the 14-3-3η markers and 96% for any one of the four markers. This represents 23% more patients identified by 14-3-3η markers alone compared to RF/ACPA, and 27% more when the four markers are used together.
Conclusion
14-3-3η markers identify 93% of early RA patients compared to RF/ACPA alone at 76%. The combination of all four markers captures 96% of early RA patients which creates the opportunity to treat more patients within the therapeutic window and improve clinical outcomes.
Disclosure:
D. van Schaardenburg,
Augurex Life Sciences Corp,
5;
W. P. Maksymowych,
Augurex Life Sciences Corp,
5;
M. Boers,
Augurex Life Sciences Corp,
5;
S. Turk,
None;
M. Murphy,
Augurex Life Sciences Corp,
3;
A. Marotta,
Augurex Life Sciences Corp.,
3.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/14-3-3%ce%b7-early-ra-biomarkers-does-seronegative-ra-exist/